Multi-organ phenotypes in mice lacking latent TGFß binding protein 2 (LTBP2).

BACKGROUND: Latent TGFß binding protein-2 (LTBP2) is a fibrillin 1 binding component of the microfibril. LTBP2 is the only LTBP protein that does not bind any isoforms of TGFß, although it may interfere with the function of other LTBPs or interact with other signaling pathways. RESULTS: Here, we investigate mice lacking Ltbp2 (Ltbp2-/- ) and identify multiple phenotypes that impact bodyweight and fat mass, and affect bone and skin development. The alterations in skin and bone development are particularly noteworthy since the strength of these tissues is differentially affected by loss of Ltbp2. Interestingly, some tissues that express high levels of Ltbp2, such as the aorta and lung, do not have a developmental or homeostatic phenotype. CONCLUSIONS: Analysis of these mice show that LTBP2 has complex effects on development through direct effects on the extracellular matrix (ECM) or on signaling pathways that are known to regulate the ECM.

Modulation of TRPV4 protects against degeneration induced by sustained loading and promotes matrix synthesis in the intervertebral disc.

While it is well known that mechanical signals can either promote or disrupt intervertebral disc (IVD) homeostasis, the molecular mechanisms for transducing mechanical stimuli are not fully understood. The transient receptor potential vanilloid 4 (TRPV4) ion channel activated in isolated IVD cells initiates extracellular matrix (ECM) gene expression, while TRPV4 ablation reduces cytokine production in response to circumferential stretching. However, the role of TRPV4 on ECM maintenance during tissue-level mechanical loading remains unknown. Using an organ culture model, we modulated TRPV4 function over both short- (hours) and long-term (days) and evaluated the IVDs' response. Activating TRPV4 with the agonist GSK101 resulted in a Ca2+ flux propagating across the cells within the IVD. Nuclear factor (NF)-κB signaling in the IVD peaked at 6 h following TRPV4 activation that subsequently resulted in higher interleukin (IL)-6 production at 7 days. These cellular responses were concomitant with the accumulation of glycosaminoglycans and increased hydration in the nucleus pulposus that culminated in higher stiffness of the IVD. Sustained compressive loading of the IVD resulted in elevated NF-κB activity, IL-6 and vascular endothelial growth factor A (VEGFA) production, and degenerative changes to the ECM. TRPV4 inhibition using GSK205 during loading mitigated the changes in inflammatory cytokines, protected against IVD degeneration, but could not prevent ECM disorganization due to mechanical damage in the annulus fibrosus. These results indicate TRPV4 plays an important role in both short- and long-term adaptations of the IVD to mechanical loading. The modulation of TRPV4 may be a possible therapeutic for preventing load-induced IVD degeneration.

Building a Partnership Between a University and Local High School to Foster and Grow Interest in Biomedical Sciences and Engineering.

To help foster interest in science, technology, engineering, and math (STEM), it is important to develop opportunities that excite and teach young minds about STEM-related fields. Over the past several years, our university-based research group has sought to help grow excitement around the biomechanics and biomedical engineering fields. The purposes of this technical brief are to (1) discuss the development of a partnership built between a St. Louis area high school and biomechanics research lab and (2) provide practical guidance for other researchers looking to implement a long-term outreach program. The partnership uses three different outreach opportunities. The first opportunity consisted of 12th-grade students visiting university research labs for an up-close perspective of ongoing biomedical research. The second opportunity was a biomedical research showcase where research-active graduate students traveled to the high school to perform demonstrations. The third opportunity consisted of a collaborative capstone project where a high school student was able to carry out research directly in a university lab. To date, we have expanded our reach from 19 students to interacting with over 100 students, which has yielded increased interest in STEM related research. Our postprogram survey showed that outreach programs such as the one described herein can increase interest in STEM within all ages of high school students. Building partnerships between high schools and university researchers increases the interest in STEM amongst high school students, and gives graduate students an outlet to present work to an eager-to-learn audience.

Adipose stem cells exhibit mechanical memory and reduce fibrotic contracture in a rat elbow injury model.

Fibrosis is driven by a misdirected cell response causing the overproduction of extracellular matrix and tissue dysfunction. Numerous pharmacological strategies have attempted to prevent fibrosis but have attained limited efficacy with some detrimental side effects. While stem cell treatments have provided more encouraging results, they have exhibited high variability and have not always improved tissue function. To enhance stem cell efficacy, we evaluated whether mechanical memory could direct cell response. We hypothesized that mechanically pre-conditioning on a soft matrix (soft priming) will delay adipose-derived stem cell (ASC) transition to a pro-fibrotic phenotype, expanding their regenerative potential, and improving healing in a complex tissue environment. Primary ASCs isolated from rat and human subcutaneous fat exhibited mechanical memory, demonstrated by a delayed cell response to stiffness following two weeks of soft priming including decreased cell area, actin coherency, and extracellular matrix production compared to cells on stiff substrates. Soft primed ASCs injected into our rat model of post-traumatic elbow contracture decreased histological evidence of anterior capsule fibrosis and increased elbow range-of-motion when evaluated by joint mechanics. These findings suggest that exploiting mechanical memory by strategically controlling the culture environment during cell expansion may improve the efficacy of stem cell-based therapies targeting fibrosis.

Implementation of a logarithmic division-of-focal-plane polarimeter to quantify changes in collagen alignment at varying levels of illumination.

We examine the impact of illumination, aperture, and sample thickness on two division-of-focal-plane (DoFP) polarimeters, one created using a standard 3 T pixel and the other with a forward-biased, logarithmic pixel. Across all measured metrics the logarithmic DoFP polarimeter was better able to track real-time changes in collagen alignment than the standard DoFP polarimeter.

Functional Measures of Grip Strength and Gait Remain Altered Long-term in a Rat Model of Post-traumatic Elbow Contracture.

Post-traumatic joint contracture (PTJC) is a debilitating condition, particularly in the elbow. Previously, we established an animal model of elbow PTJC quantifying passive post-mortem joint mechanics and histological changes temporally. These results showed persistent motion loss similar to what is experienced in humans. Functional assessment of PTJC in our model was not previously considered; however, these measures would provide a clinically relevant measure and would further validate our model by demonstrating persistently altered joint function. To this end, a custom bilateral grip strength device was developed, and a recently established open-source gait analysis system was used to quantify forelimb function in our unilateral injury model. In vivo joint function was shown to be altered long-term and never fully recover. Specifically, forelimb strength in the injured limbs showed persistent deficits at all time points; additionally, gait patterns remained imbalanced and asymmetric throughout the study (although a few gait parameters did return to near normal levels). A quantitative understanding of these longitudinal, functional disabilities further strengthens the clinical relevance of our rat PTJC model enabling assessment of the effectiveness of future interventions aimed at reducing or preventing PTJC.

Biomechanical comparison of docking ulnar collateral ligament reconstruction with and without an internal brace.

BACKGROUND: Current ulnar collateral ligament (UCL) reconstruction techniques are substantially less stiff and demonstrate lower load to failure compared with the native UCL. UCL repair with the addition of an internal brace has demonstrated superior biomechanical performance compared with docking UCL reconstruction, but internal bracing has not yet been used in UCL reconstruction. HYPOTHESIS/PURPOSE: To evaluate the time-zero biomechanical performance of a UCL docking technique reconstruction with and without an internal brace compared with native UCL properties. METHODS: Twelve matched pairs of cadaveric elbows were dissected and fixed at 90° for biomechanical testing. A cyclic valgus torque protocol was used to test the anterior band of the UCL in native specimens. After native specimens were failed, palmaris grafts were used for a docking reconstruction with or without internal brace and were subjected to the same valgus torque test protocol. Torsional stiffness, ultimate failure torque, and ulnohumeral gapping were determined. RESULTS: Stiffness in UCL reconstructions using a standard docking technique (3.0 ± 0.4 N m/deg) were significantly less stiff (P < .001) than native UCL (4.0 ± 0.8 N m/deg), whereas reconstructions using an internal brace (3.6 ± 0.6 N m/deg) were not different (P = .120) compared with native. Ultimate failure torque for standard docking (18.3 ± 4.1 N m) was significantly lower (P < .001) than native UCL (36.9 ± 10.1 N m), whereas the internal brace samples (35.3 ± 9.8 N m) were not different (P = .772) than native. CONCLUSION: UCL reconstruction with an internal brace augmentation provides superior stiffness and time-zero failure strength when compared with the standard docking technique.

Scatter Artifact with Ga-68-PSMA-11 PET: Severity Reduced With Furosemide Diuresis and Improved Scatter Correction.

PURPOSE: To assess the utility of furosemide diuresis and the role of an improved scatter correction algorithm in reducing scatter artifact severity on Ga-68- Prostate-specific membrane antigen (PSMA)-11 positron emission tomography (PET). MATERIALS AND METHODS: A total of 139 patients underwent Ga-68-PSMA-11 PET imaging for prostate cancer: 47 non-time-of-flight (non-TOF) PET/computed tomography, 51 PET/magnetic resonance imaging (MRI) using the standard TOF scatter correction algorithm, and 41 PET/MRI using an improved TOF scatter correction algorithm. Whole-body PET acquisitions were subdivided into 3 regions: around kidneys; between kidneys and bladder; and around bladder. The images were reviewed, and scatter artifact severity was rated using a Likert-type scale. RESULTS: The worst scatter occurred when using non-TOF scatter correction without furosemide, where 42.1% of patients demonstrated severe scatter artifacts in 1 or more regions. Improved TOF scatter correction resulted in the smallest percentage of studies with severe scatter (6.5%). Scatter ratings by region were lowest using improved TOF scatter correction. Furosemide reduced mean scatter severity when using non-TOF and standard TOF. CONCLUSIONS: Both furosemide and scatter correction algorithm play a role in reducing scatter in PSMA PET. Improved TOF scatter correction resulted in the lowest scatter severity.

Muscle does not drive persistent posttraumatic elbow contracture in a rat model.

INTRODUCTION: Posttraumatic elbow contracture is clinically challenging because injury often disrupts multiple periarticular soft tissues. Tissue specific contribution to contracture, particularly muscle, remains poorly understood. METHODS: In this study we used a previously developed animal model of elbow contracture. After surgically inducing a unilateral soft tissue injury, injured limbs were immobilized for 3, 7, 21, and 42 days (IM) or for 42 IM with 42 days of free mobilization (42/42 IM-FM). Biceps brachii active/passive mechanics and morphology were evaluated at 42 IM and 42/42 IM-FM, whereas biceps brachii and brachialis gene expression was evaluated at all time points. RESULTS: Injured limb muscle exhibited significantly altered active/passive mechanics and decreased fiber area at 42 IM but returned to control levels by 42/42 IM-FM. Gene expression suggested muscle growth rather than a fibrotic response at 42/42 IM-FM. DISCUSSION: Muscle is a transient contributor to motion loss in our rat model of posttraumatic elbow contracture. Muscle Nerve 58:843-851, 2018.

Multiscale mechanical effects of native collagen cross-linking in tendon.

The hierarchical structure of tendon allows for attenuation of mechanical strain down decreasing length scales. While reorganization of collagen fibers accounts for microscale strain attenuation, cross-linking between collagen molecules contributes to deformation mechanisms at the fibrillar and molecular scales. Divalent and trivalent enzymatic cross-links form during the development of collagen fibrils through the enzymatic activity of lysyl oxidase (LOX). By establishing connections between telopeptidyl and triple-helical domains of adjacent molecules within collagen fibrils, these cross-links stiffen the fibrils by resisting intermolecular sliding. Ultimately, greater enzymatic cross-linking leads to less compliant and stronger tendon as a result of stiffer fibrils. In contrast, nonenzymatic cross-links such as glucosepane and pentosidine are not produced during development but slowly accumulate through glycation of collagen. Therefore, these cross-links are only expected to be present in significant quantities in advanced age, where there has been sufficient time for glycation to occur, and in diabetes, where the presence of more free sugar in the extracellular matrix increases the rate of glycation. Unlike enzymatic cross-links, current evidence suggests that nonenzymatic cross-links are at least partially isolated to the surface of collagen fibers. As a result, glycation has been proposed to primarily impact tendon mechanics by altering molecular interactions at the fiber interface, thereby diminishing sliding between fibers. Thus, increased nonenzymatic cross-linking decreases microscale strain attenuation and the viscous response of tendon. In conclusion, enzymatic and nonenzymatic collagen cross-links have demonstrable and distinct effects on the mechanical properties of tendon across different length scales.

Combined in vivo and ex vivo analysis of mesh mechanics in a porcine hernia model.

BACKGROUND: Hernia meshes exhibit variability in mechanical properties, and their mechanical match to tissue has not been comprehensively studied. We used an innovative imaging model of in vivo strain tracking and ex vivo mechanical analysis to assess effects of mesh properties on repaired abdominal walls in a porcine model. We hypothesized that meshes with dissimilar mechanical properties compared to native tissue would alter abdominal wall mechanics more than better-matched meshes. METHODS: Seven mini-pigs underwent ventral hernia creation and subsequent open repair with one of two heavyweight polypropylene meshes. Following mesh implantation with attached radio-opaque beads, fluoroscopic images were taken at insufflation pressures from 5 to 30 mmHg on postoperative days 0, 7, and 28. At 28 days, animals were euthanized and ex vivo mechanical testing performed on full-thickness samples across repaired abdominal walls. Testing was conducted on 13 mini-pig controls, and on meshes separately. Stiffness and anisotropy (the ratio of stiffness in the transverse versus craniocaudal directions) were assessed. RESULTS: 3D reconstructions of repaired abdominal walls showed stretch patterns. As pressure increased, both meshes expanded, with no differences between groups. Over time, meshes contracted 17.65% (Mesh A) and 0.12% (Mesh B; p = 0.06). Mesh mechanics showed that Mesh A deviated from anisotropic native tissue more than Mesh B. Compared to native tissue, Mesh A was stiffer both transversely and craniocaudally. Explanted repaired abdominal walls of both treatment groups were stiffer than native tissue. Repaired tissue became less anisotropic over time, as mesh properties prevailed over native abdominal wall properties. CONCLUSIONS: This technique assessed 3D stretch at the mesh level in vivo in a porcine model. While the abdominal wall expanded, mesh-ingrown areas contracted, potentially indicating stresses at mesh edges. Ex vivo mechanics demonstrate that repaired tissue adopts mesh properties, suggesting that a better-matched mesh could reduce changes to abdominal wall mechanics.

Temporal Patterns of Motion in Flexion-extension and Pronation-supination in a Rat Model of Posttraumatic Elbow Contracture.

BACKGROUND: The elbow is highly susceptible to contracture, which affects up to 50% of patients who experience elbow trauma. Previously, we developed a rat model to study elbow contracture that exhibited features similar to the human condition, including persistently decreased ROM and increased capsule thickness/adhesions. However, elbow ROM was not quantitatively evaluated over time throughout contracture development and subsequent mobilization of the joint. QUESTIONS/PURPOSES: The purposes of this study were (1) to quantify the time-dependent mechanics of contracture, including comparison of contracture after immobilization and free mobilization; and (2) to determine what changes occur in capsule and joint surface morphology that may support the altered joint mechanics. METHODS: A total of 96 male Long-Evans rats were randomized into control and injury (unilateral soft tissue injury/immobilization) groups. Flexion-extension and pronation-supination joint mechanics (n = 8/group) were evaluated after 3, 7, 21, or 42 days of immobilization (IM) or after 42 days of IM with either 21 or 42 days of free mobilization (63 or 84 FM, respectively). After measuring joint mechanics, a subset of these limbs (n = 3/group) was prepared for histologic analysis and blinded sections were scored to evaluate capsule and joint surface morphology. Joint mechanics and capsule histology at 42 IM and 84 FM were reported previously but are included to demonstrate the full timeline of elbow contracture. RESULTS: In flexion-extension, injured limb ROM was decreased compared with control (103° ± 11°) by 21 IM (70° ± 13°) (p = 0.001). Despite an increase in injured limb ROM from 42 IM (55° ± 14°) to 63 FM (83° ± 10°) (p < 0.001), injured limb ROM was still decreased compared with control (103° ± 11°) (p = 0.002). Interestingly, ROM recovery plateaued because there was no difference between injured limbs at 63 (83° ± 10°) and 84 FM (73° ± 19°) (p > 0.999). In pronation-supination, increased injured limb ROM occurred until 7 IM (202° ± 32°) compared with control (155° ± 22°) (p = 0.001), representative of joint instability. However, injured limb ROM decreased from 21 (182° ± 25°) to 42 IM (123° ± 47°) (p = 0.001), but was not different compared with control (155° ± 22°) (p = 0.108). Histologic evaluation showed morphologic changes in the anterior capsule (increased adhesions, myofibroblasts, thickness) and nonopposing joint surfaces (surface irregularities with tissue overgrowth, reduced matrix), but these changes did not increase with time. CONCLUSIONS: Overall, flexion-extension and pronation-supination exhibited distinct time-dependent patterns during contracture development and joint mobilization. Histologic evaluation showed tissue changes, but did not fully explain the patterns in contracture mechanics. Future work will use this rat model to evaluate the periarticular soft tissues of the elbow to isolate tissue-specific contributions to contracture to ultimately develop strategies for tissue-targeted treatments. CLINICAL RELEVANCE: A rat model of posttraumatic elbow contracture quantitatively described contracture development/progression and reiterates the need for rehabilitation strategies that consider both flexion-extension and pronation-supination elbow motion.

Multiscale Mechanical Evaluation of Human Supraspinatus Tendon Under Shear Loading After Glycosaminoglycan Reduction.

Proteoglycans (PGs) are broadly distributed within many soft tissues and, among other roles, often contribute to mechanical properties. Although PGs, consisting of a core protein and glycosaminoglycan (GAG) sidechains, were once hypothesized to regulate stress/strain transfer between collagen fibrils and help support load in tendon, several studies have reported no changes to tensile mechanics after GAG depletion. Since GAGs are known to help sustain nontensile loading in other tissues, we hypothesized that GAGs might help support shear loading in human supraspinatus tendon (SST), a commonly injured tendon which functions in a complex multiaxial loading environment. Therefore, the objective of this study was to determine whether GAGs contribute to the response of SST to shear, specifically in terms of multiscale mechanical properties and mechanisms of microscale matrix deformation. Results showed that chondroitinase ABC (ChABC) treatment digested GAGs in SST while not disrupting collagen fibers. Peak and equilibrium shear stresses decreased only slightly after ChABC treatment and were not significantly different from pretreatment values. Reduced stress ratios were computed and shown to be slightly greater after ChABC treatment compared to phosphate-buffered saline (PBS) incubation without enzyme, suggesting that these relatively small changes in stress values were not due strictly to tissue swelling. Microscale deformations were also not different after ChABC treatment. This study demonstrates that GAGs possibly play a minor role in contributing to the mechanical behavior of SST in shear, but are not a key tissue constituent to regulate shear mechanics.

Validation of Single C-Arm Fluoroscopic Technique for Measuring In Vivo Abdominal Wall Deformation.

Hernia meshes significantly reduce the recurrence rates in hernia repair. It is known that they affect the abdominal wall postimplantation, yet the understanding of in vivo mechanics in the mesh placement area is lacking. We established a single C-arm biplane fluoroscopic system to study strains at the interface between the mesh and repaired abdominal tissues. We aimed to validate this system for future porcine hernia repair studies. Custom matlab programs were written to correct for pincushion distortion, and direct linear transformation (DLT) reconstructed objects in 3D. Using a custom biplane-trough setup, image sets were acquired throughout the calibrated volume to evaluate a radio-opaque test piece with known distances between adjacent beads. Distances were measured postprocessing and compared to known measurements. Repeatability testing was conducted by taking image sets of the test piece in a fixed location to determine system movement. The error in areal stretch tracking was evaluated by imaging a square plate with fixed radio-opaque beads and using matlab programs to compare the measured areal stretch to known bead positions. Minor differences between measured and known distances in the test piece were not statistically different, and the system yielded a 0.01 mm bias in the XY plane and a precision of 0.61 mm. The measured areal stretch was 0.996, which was not significantly different than the expected value of 1. In addition, preliminary stretch data for a hernia mesh in a porcine model demonstrated technique feasibility to measure in vivo porcine abdominal mechanics.

Pronation-Supination Motion Is Altered in a Rat Model of Post-Traumatic Elbow Contracture.

The elbow joint is highly susceptible to joint contracture, and treating elbow contracture is a challenging clinical problem. Previously, we established an animal model to study elbow contracture that exhibited features similar to the human condition including persistent decreased range of motion (ROM) in flexion-extension and increased capsule thickness/adhesions. The objective of this study was to mechanically quantify pronation-supination in different injury models to determine if significant differences compared to control or contralateral persist long-term in our animal elbow contracture model. After surgically inducing soft tissue damage in the elbow, Injury I (anterior capsulotomy) and Injury II (anterior capsulotomy with lateral collateral ligament transection), limbs were immobilized for 6 weeks (immobilization (IM)). Animals were evaluated after the IM period or following an additional 6 weeks of free mobilization (FM). Total ROM for pronation-supination was significantly decreased compared to the uninjured contralateral limb for both IM and FM, although not different from control limbs. Specifically, for both IM and FM, total ROM for Injury I and Injury II was significantly decreased by ∼20% compared to contralateral. Correlations of measurements from flexion-extension and pronation-supination divulged that FM did not affect these motions in the same way, demonstrating that joint motions need to be studied/treated separately. Overall, injured limbs exhibited persistent motion loss in pronation-supination when comparing side-to-side differences, similar to human post-traumatic joint contracture. Future work will use this animal model to study how elbow periarticular soft tissues contribute to contracture.

Functionally Distinct Tendons From Elastin Haploinsufficient Mice Exhibit Mild Stiffening and Tendon-Specific Structural Alteration.

Elastic fibers are present in low quantities in tendon, where they are located both within fascicles near tenocytes and more broadly in the interfascicular matrix (IFM). While elastic fibers have long been known to be significant in the mechanics of elastin-rich tissue (i.e., vasculature, skin, lungs), recent studies have suggested a mechanical role for elastic fibers in tendons that is dependent on specific tendon function. However, the exact contribution of elastin to properties of different types of tendons (e.g., positional, energy-storing) remains unknown. Therefore, this study purposed to evaluate the role of elastin in the mechanical properties and collagen alignment of functionally distinct supraspinatus tendons (SSTs) and Achilles tendons (ATs) from elastin haploinsufficient (HET) and wild type (WT) mice. Despite the significant decrease in elastin in HET tendons, a slight increase in linear stiffness of both tendons was the only significant mechanical effect of elastin haploinsufficiency. Additionally, there were significant changes in collagen nanostructure and subtle alteration to collagen alignment in the AT but not the SST. Hence, elastin may play only a minor role in tendon mechanical properties. Alternatively, larger changes to tendon mechanics may have been mitigated by developmental compensation of HET tendons and/or the role of elastic fibers may be less prominent in smaller mouse tendons compared to the larger bovine and human tendons evaluated in previous studies. Further research will be necessary to fully elucidate the influence of various elastic fiber components on structure-function relationships in functionally distinct tendons.

Persistent motion loss after free joint mobilization in a rat model of post-traumatic elbow contracture.

BACKGROUND: Post-traumatic joint contracture (PTJC) in the elbow is a challenging clinical problem due to the anatomical and biomechanical complexity of the elbow joint. METHODS: We previously established an animal model to study elbow PTJC, wherein surgically induced soft tissue damage, followed by 6 weeks of unilateral immobilization in Long-Evans rats, led to stiffened and contracted joints that exhibited features similar to the human condition. In this study, after 6 weeks of immobilization, we remobilized the animal (ie, external bandage removed and free cage activity) for an additional 6 weeks, after which the limbs were evaluated mechanically and histologically. The objective of this study was to evaluate whether this decreased joint motion would persist after 6 weeks of free mobilization (FM). RESULTS: After FM, flexion-extension demonstrated decreased total range of motion (ROM) and neutral zone length, and increased ROM midpoint for injured limbs compared with control and contralateral limbs. Specifically, after FM total ROM demonstrated a significant decrease of approximately 22% and 26% compared with control and contralateral limbs for injury I (anterior capsulotomy) and injury II (anterior capsulotomy with lateral collateral ligament transection), respectively. Histologic evaluation showed increased adhesion, fibrosis, and thickness of the capsule tissue in the injured limbs after FM compared with control and contralateral limbs, which is consistent with patterns previously reported in human tissue. CONCLUSION: Even with FM, injured limbs in this model demonstrate persistent joint motion loss and histologic results similar to the human condition. Future work will use this animal model to investigate the mechanisms responsible for PTJC and responses to therapeutic intervention.

Vascular biomechanical properties in mice with smooth muscle specific deletion of Ndst1.

Heparan sulfate proteoglycans act as co-receptors for many chemokines and growth factors. The sulfation pattern of the heparan sulfate chains is a critical regulatory step affecting the binding of chemokines and growth factors. N-deacetylase-N-sulfotransferase1 (Ndst1) is one of the first enzymes to catalyze sulfation. Previously published work has shown that HSPGs alter tangent moduli and stiffness of tissues and cells. We hypothesized that loss of Ndst1 in smooth muscle would lead to significant changes in heparan sulfate modification and the elastic properties of arteries. In line with this hypothesis, the axial tangent modulus was significantly decreased in aorta from mice lacking Ndst1 in smooth muscle (SM22αcre(+)Ndst1(-/-), p < 0.05, n = 5). The decrease in axial tangent modulus was associated with a significant switch in myosin and actin types and isoforms expressed in aorta and isolated aortic vascular smooth muscle cells. In contrast, no changes were found in the compliance of smaller thoracodorsal arteries of SM22αcre(+)Ndst1(-/-) mice. In summary, the major findings of this study were that targeted ablation of Ndst1 in smooth muscle cells results in altered biomechanical properties of aorta and differential expression of myosin and actin types and isoforms.

Bioinspired Polarization Imaging Sensors: From Circuits and Optics to Signal Processing Algorithms and Biomedical Applications: Analysis at the focal plane emulates nature's method in sensors to image and diagnose with polarized light.

In this paper, we present recent work on bioinspired polarization imaging sensors and their applications in biomedicine. In particular, we focus on three different aspects of these sensors. First, we describe the electro-optical challenges in realizing a bioinspired polarization imager, and in particular, we provide a detailed description of a recent low-power complementary metal-oxide-semiconductor (CMOS) polarization imager. Second, we focus on signal processing algorithms tailored for this new class of bioinspired polarization imaging sensors, such as calibration and interpolation. Third, the emergence of these sensors has enabled rapid progress in characterizing polarization signals and environmental parameters in nature, as well as several biomedical areas, such as label-free optical neural recording, dynamic tissue strength analysis, and early diagnosis of flat cancerous lesions in a murine colorectal tumor model. We highlight results obtained from these three areas and discuss future applications for these sensors.

128-Slice dual source coronary CTA: defining optimal arterial enhancement levels.

This study aims to correlate coronary artery enhancement levels with quality of vessel visualization and calcified plaque visualization using a 128-slice dual-source CT (DSCT) scanner. Coronary CT angiography exams from 52 patients, mean age of 55 years (range, 22-90) and mean weight of 184 lbs (range, 120-320 lbs), were reviewed retrospectively. Contrast infusion rates ranged from 4.5 to 7 mL/s (mean, 5.8 mL/s). Postcontrast density of the largest calcified plaque and postcontrast density of the left main (LM) and right coronary arteries (RCA) were recorded. Enhancement quality was graded as 1=suboptimal, 2=adequate for diagnosis, and 3=excellent. Pre- and postcontrast acquisitions were compared for calcified plaque conspicuity. The largest calcified plaque density was a mean of 862 HU (range, 376 to 1,384 HU) on the postcontrast scan. The mean LM and RCA coronary artery enhancement levels for studies of excellent enhancement quality (N=43) were 468 and 457 HU, respectively, higher than mean enhancement levels of 320 and 322 HU for adequate enhancement quality (N=8) (p<0.0001 and 0.009). One study was graded as a nondiagnostic enhancement quality. Twenty-five subjects had calcified plaque, 3/8 with adequate and 22/43 with excellent enhancement quality. At least one calcified plaque measuring <2 mm was isodense to contrast enhancement on axial images in 5/25; all five were in the highest enhancement quality group. High coronary artery enhancement quality using 128-DSCT is associated with mean proximal coronary artery enhancement levels over 400 HU. High levels of enhancement may obscure small, calcified plaques.